One compact disc that includes a Computer Program Listing Appendix has been submitted in duplicate in the present application. The size of the files contained in the Computer Program Listing Appendix, their date of creation, their time of creation, and their name are found in Table 1 below. In Table 1, each row represents a file or directory. If the row represents a directory, the designation xe2x80x9c less than DIR greater than xe2x80x9d is provided in column one. If the row represents a file, the size of the file in bytes is provided in column one. Columns two and three respectively represent the date and time of file or directory creation while the fourth column represents the name of the file or directory.
The Computer Program Listing Appendix disclosed in Table 1 is hereby incorporated by reference.
This invention relates generally to a software program and method that converts a back-end clinical definition, defining a data structure and legacy data entry forms for data entry into a clinical data management system, to a front-end study definition. The front-end study definition includes a set of forms used by a Remote.
Data Entry (RDE) application to collect clinical data. The present invention further includes a method and apparatus for retrieving clinical data from RDE applications and feeding the data, on an automated basis, to the back-end clinical data management system.
Before a new drug may be sold in many countries of the world, regulatory approval must be granted. One of the most expensive and difficult aspects of obtaining this regulatory approval is the presentation of statistically significant data from clinical trials. Typically, clinical trials used to support a new drug application are divided into three or more phases, the most prominent of which are phases I, II, and III.
Phase I studies are primarily concerned with assessing the safety of a drug. Phase I testing in humans is typically done in about 20 to 100 healthy volunteers. A phase I clinical study is designed to determine what happens to the drug in the patient. That is, how it is absorbed, metabolized, and excreted. In addition, by measuring the side effects of the drug at various dosage levels, a phase I study provides information on optimal drug dosage.
While a phase I study is directed to drug safety, a phase II clinical trial is directed to drug efficacy. A phase II study occurs after successful completion of a phase I study. A phase II clinical study may last from several months to two years, and involve up to several hundred patients at numerous clinical sites throughout the world. Most phase II studies are randomized trials. One group of patients receives the experimental drug while a control group receives a placebo. Often phase II studies are xe2x80x9cblindedxe2x80x9d in the sense that neither the patients nor the researchers know who is getting the experimental drug. In this manner, the phase II study can provide a pharmaceutical company and a regulatory body, such as the United States Food and Drug Administration (FDA) of the United States or the European Commission (EC) of the European Union, comparative information about the efficacy of the new drug. If the phase II study is successful, a phase III study may be authorized.
Typically, in a phase III study, the new drug is tested in several hundred to several thousand patients at hundreds of clinical sites throughout the world. This large-scale testing provides the pharmaceutical company and the regulatory agency with a more thorough understanding of the drug""s effectiveness, benefits, and the range of possible adverse reactions. Most phase III studies are randomized and blinded trials. Phase III studies typically last several years. Once a phase III study is successfully completed, a pharmaceutical company can request regulatory approval for marketing the new drug.
The resources needed to support a complex multi-site phase II or phase III clinical are staggering. Trained professionals must administer the new drug under the exact requirements of the protocols of the clinical study and intricate patient records must be maintained. The clinical trial protocol may require numerous patient visits over an extended period of time. Any error in the patient record could result in patient data disqualification.
Because of the complexity of the protocols used in clinical trials, the amount of information that must be tracked requires the capabilities of a back-end clinical data management system (CDMS). Representative back-end clinical data management systems include Clintrial 4.3, (Clinsoft Corporation, Lexington, Mass., www.clinsoft.net), and Oracle Clinical (O/C), Oracle Inc., Redwood Shores, Calif., www.oracle.com). These back-end clinical data management systems typically provide sophisticated tools such as, a batch validation engine, a batch data loader, a randomization system, a thesaurus management system, and a lab reference range system. However, because a clinical trial may be conducted at hundreds of sites throughout the world, it is impracticable to place a back-end CDMS at each clinical site. The problem of routing clinical data into a back-end CDMS has therefore been addressed by a number of different approaches in the art.
A traditional approach to routing clinical data to a back-end CDMS is to gather clinical data at each site using paper-based forms designed in accordance with the specifications of a clinical trial. At a later date, the paper-based forms are manually entered twice into a computer. This double-entry is requested in order to compare the two data sets in order to check for data entry errors. While this approach is functional, it is unsatisfactory. Electronic data entry based on the paper-based forms is often done at a site that is remote from the clinical setting, making it difficult to consult the clinician if there is a problem with the content of the paper-based forms. Because of the exact requirements of the clinical trial protocol, such unresolved errors typically result in patient disqualification. Another problem with paper-based forms is that the information is essentially processed twice, first, when the data is entered on the paper-based form and, second, when the electronic data entry is done based on the content of the paper-base forms. This effectively doubles the chance of error in the data entry process. Yet another problem with paper based forms is that there is considerable delay before the clinical data is available is review because a sponsor needs to wait until the clinical data is entered into the back-end database before electronic analysis may be run on the clinical data.
To address the problems with traditional approaches to clinical data entry into a legacy CDMS, an entire industry of Remote Data Entry (RDE) products has developed. Representative vendors in this industry include InferMed, Ltd., London UK, (www.infermed.com), Phase Forward Inc., Waltham, Mass., (www.phaseforward.com), CB Technology, Philadelphia, Pa., (www.cbtech.com), DataTRAK Cleveland, Ohio, (www.datatraknet.com), and Araccel, Stockholm, Sweden, (www.araccel.com), and TEAMworks, Hannover, Germany (www.teamworks.de). These RDE products are also termed front-end data acquisition products. RDE products provide capabilities for making electronic clinical data entry forms that are used on a client computer, such as a laptop, at the clinical site. Data collected using an RDE product are sent electronically to a centralized back-end CDMS where statistical analysis is performed on the clinical data to ascertain drug efficacy and/or safety.
RDE products are advantageous because they prevent discrepancies during data entry. An RDE product provides electronic case report forms (eCRFs) to the data entrant for entry of clinical data. The eCRF is capable of containing data validation checks that show a warning in the case when incorrect or xe2x80x9cout of the programmed rangexe2x80x9d entries are received. The data entrant can then correct the problem with the data entry immediately. In addition the eCRF provides xe2x80x9cprotocol guidance.xe2x80x9d For example, pregnancy test questions are only displayed to the data entrant when the patient has indicated that she is female.
While RDE products represent an advance over the paper-based form approach, they are unsatisfactory. RDE products require a custom study definition to be prepared for each clinical trial. For example, MACRO from InferMed, Ltd., London UK, requires that a macro study definition be prepared for each clinical trial monitored by MACRO. The macro study definition is a collection of metatables that describe the patient data collected at a clinical site. The macro study definition may also include the format of the electronic forms used to acquire the clinical data as well as other pertinent data acquisition components.
In the art, a clinical definition must be set up for the back-end CDMS. The back-end clinical definition is a data structure that is used to track all the patients in a clinical study. The back-end clinical definition is designed in accordance with the specifications of the particular back-end CDMS used to support a particular clinical study. The problem with the RDE custom study definitions and the back-end clinical definitions becomes apparent when one tries to interface the RDE custom study definition to the back-end clinical definition. Because there are no industry standards for RDE study definitions and back-end clinical definitions, significant custom programming is needed for each clinical study, in order to allow an RDE system to electronically feed data to a back-end CDMS.
A third approach to addressing the problem of clinical data entry is to provide a web page interface to a back-end CDMS. An example of a product that uses this approach is Oracle Clinical Remote Data Capture v4i, Oracle Inc., Redwood Shores, Calif. In this approach, each clinical site includes a client computer with a standard web browser. The web browser is used to load into the client computer a data entry form from a remote web server. Clinical data are then entered into the data entry form. Advantageously, the data entered into the web-based data entry form may be electronically entered directly into the back-end CDMS. While the third approach eliminates the need to interface a front-end study definition with a back-end clinical definition, this approach is still unsatisfactory. First, the client computer must be connected to the back-end CDMS by a long-distance network throughout data entry. This requirement limits how the web page interface may be constructed and deployed. Another disadvantage to using a long-distance network throughout data entry are the issues of network latency, network bandwidth limitations, and server load that are inevitably raised. These issues conspire to make data entry a frustrating experience. In fact, it is widely appreciated that data entry using a web page driven by a remote server requires tremendous patience. For example, consider the amount of patience required to enter personal data at an Internet web site, such as www.amazon.com, in order to register at the site. Clinical data entry using a web page system, such as Oracle Clinical Remote Data Capture v4i, is comparable to registering hundreds to thousands of people at a site such as www.amazaon.com or www.gap.com on a periodic basis over an extended period of time.
Yet another disadvantage of using a web page interface to a back-end CDMS is that back-end CDMS interfaces are designed for data-entry clerks. Therefore, they lack support for the tools necessary to ensure that clinical trial protocol is followed. Such tools include protocol violation alerts, enforced eligibility, and protocol recommendations regarding dosing or test procedures. Furthermore, direct data entry into a back-end CDMS using a web-page introduces questionable practices. Back-end CDMS interfaces are designed to facilitate data entry by data-entry clerks. As such, many of the fields in the data entry forms have defaulted answers. While the use of defaulted answers is appropriate for routine data-entry, it is not appropriate for forms that are considered source documents. A source document represents the form that records actual clinical observations. In order to ensure that all clinical observations mandated by a clinical protocol are actually made, the source form should not have defaulted answers.
In view of these difficulties, what is needed in the art is a system and method for collecting clinical data without the many drawbacks found in preexisting systems and methods.
The present invention provides novel solutions to the drawbacks found in the art. In particular, the present invention uses a back-end clinical definition developed in accordance with a legacy back-end CDMS to generate a set of forms, also termed a front-end study definition, that can be used by a front-end Remote Data Entry (RDE) product. A clinical worker designs a back-end clinical definition using a back-end CDMS. Then, using the instant invention, the back-end clinical definition is converted into a front-end study definition. The front-end study definition is transferred to each computer hosting a front-end data RDE product in a clinical trial. The front-end RDE product uses the front-end study definition to regulate the acquisition of clinical data. The front-end study definition includes the description of a set of forms that are used by a data entrant to enter clinical data.
During the process of converting a back-end clinical definition to a front-end study definition, a novel conversion map is created. The conversion map allows for the conversion of clinical data acquired with the RDE product to a format that can be electronically read by a back-end CDMS. In one embodiment of the present invention, clinical data acquired using the front-end RDE product is converted into a novel front-end data packet that can be electronically imported into the legacy back-end CDMS. In this way, data can be acquired without independently creating a back-end clinical definition and a front-end study definition and tediously resolving conflicts between the two definitions. Furthermore, the instant invention allows front-end data to be acquired in real-time without the use of time consuming Internet driven menus that attempt to pipe data directly into a back-end CDMS over the Internet using web page-based data entry screens.
One aspect of the present invention provides a method for defining a front-end study definition based on a back-end clinical definition. In the method, a conversion map is created for matching a set of first components in the back-end clinical definition with a set of second components in the front-end study definition. Each of the first components in the set of first components in the back-end clinical definition is parsed. This parsing step involves: (i) adding an identifier to the conversion map that corresponds to the first component, (ii) editing the front-end study definition to include a second component that corresponds to the first component and, (iii) revising the conversion map to include the identity of the second component in the front-end study definition that corresponds with the first component. When the parsing step is completed, the conversion map includes a record of matching first and second components in the back-end clinical definition and the corresponding front-end study definition. In one embodiment of the present invention the back-end study definition is an Oracle Clinical definition and the front-end study definition is a macro study definition.
Another aspect of the present invention provides a computer readable memory that is used to direct a client/server system to function in a specified manner. The computer readable memory includes a back-end CDMS that is capable of saving data in accordance with a back-end clinical definition. The memory further includes a Remote Data Entry module for collecting clinical data in accordance with a front-end study definition. The memory also includes a mapper server module for converting the back-end clinical definition into a corresponding front-end study definition. The study definition module includes executable instructions stored in the computer readable memory that include:
instructions for creating a conversion map that matches a set of first components in the back-end clinical definition with a set of second components in the corresponding front-end study definition; and
instructions for parsing each of the first components in the set of first components in the back-end clinical definition, wherein, for each of these first components in the set of first components, the instructions for parsing comprise:
(i) instructions for adding an identifier to the conversion map that corresponds to the first component;
(ii) instructions for editing the corresponding front-end study definition to include a second component that corresponds to the first component; and
(iii) instructions for revising the conversion map to include the identity of the second component in the front-end study definition that corresponds with the first component.
When the instructions for parsing are completed, the conversion map includes a record of matching first and second components in the back-end clinical definition and the corresponding front-end study definition.
Yet another aspect of the present invention provides a method for storing clinical data in a back-end CDMS in accordance with a back-end clinical definition. In this method, a front-end data packet is obtained from a Remote Data Entry module. The Remote Data Entry module collects the clinical data in accordance with a front-end study definition. Then the front-end data packet is parsed. For each patient in the front-end data packet, this parsing step comprises adding front-end study definition/back-end clinical definition match data for the patient to a conversion map. Once all the patients are parsed, the conversion map is used to construct a back-end data packet that is uploaded to the back-end CDMS. In some embodiments, the parsing step further comprises verifying that clinical identifiers have been set for the patient, wherein, when the clinical identifiers have not been set for said patient, data in the front-end data packet associated with the patient is rejected. In some embodiments of the present invention, the back-end study definition is an Oracle Clinical definition and the front-end study definition is a macro study definition.